The proposed studies are designed to evaluate the influence of acid-base disturbaces on fluoride metabolism and toxicity in rats and dogs. It has been established that the renal clearance of fluoride is a positive function of urinary pH. The transport process is best described in terms of the nonionic diffusion of hydrogen fluoride according to the pH gradient across adjacent fluid compartments. Pre-existing alkalosis was found to provide significant protection against acute fluoride toxicity while pre-existing acidosis was found to potentiate the toxicity. The chronic balance of fluoride was more positive when the animals were acidotic and this resulted in elevated tissue fluoride throughout the body.